Molecular mechanism of CASC5 promoting breast cancer development through BUB1

HE Gui-sheng; CHEN Heng-yu; LYU Xiao-ling; SONG Tao; CHEN Xiu-xiu; FU Guang-hua; WU Huang-fu; CHEN Yun-jing; SU Ya-jing; ZHENG Wu-ping

doi:10.11659/jjssx.07E022085

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Molecular mechanism of CASC5 promoting breast cancer development through BUB1

Basic Research | 更新时间：2023-04-24

- Molecular mechanism of CASC5 promoting breast cancer development through BUB1
- JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY Vol. 32, Issue 4, Pages: 297-302(2023)
- 作者机构：
  
  1.海南医学院第二附属医院乳甲外科，海南海口 570100
  2.海南医学院第二附属医院耳鼻喉科，海南海口 570100
  3.中国人民解放军联勤保障部队第九二八医院普外科，海南海口 571199
- 作者简介：
- 基金信息：
- DOI：10.11659/jjssx.07E022085
  CLC： R737.9
- Published：25 April 2023，
  
  Received：22 July 2022，
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何贵省,陈恒余,吕小玲等.CASC5通过BUB1促进乳腺癌发生发展的分子机制研究[J].局解手术学杂志,2023,32(04):297-302.

HE Gui-sheng,CHEN Heng-yu,LYU Xiao-ling,et al.Molecular mechanism of CASC5 promoting breast cancer development through BUB1[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2023,32(04):297-302.
何贵省,陈恒余,吕小玲等.CASC5通过BUB1促进乳腺癌发生发展的分子机制研究[J].局解手术学杂志,2023,32(04):297-302. DOI： 10.11659/jjssx.07E022085.

HE Gui-sheng,CHEN Heng-yu,LYU Xiao-ling,et al.Molecular mechanism of CASC5 promoting breast cancer development through BUB1[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2023,32(04):297-302. DOI： 10.11659/jjssx.07E022085.

摘要

目的

探究易感性癌症候选基因5（CASC5）对乳腺癌发生发展的作用及其相关机制。

方法

收集50例乳腺癌患者的肿瘤组织及其癌旁组织，采用qRT-PCR检测CASC5的表达水平，并分析其与患者临床病理特征的关系。通过脂质体转染法将si-CASC5、si-BUB1和si-NC转染至MDA-MB-231和MCF-7细胞，采用qRT-PCR和Western blot检测细胞CASC5、BUB1表达水平，CCK-8检测细胞增殖能力，Transwell检测细胞侵袭能力。利用String数据库分析CASC5相关蛋白，并在MCF7细胞中验证。通过免疫共沉淀检测CASC5与BUB1的结合情况，qRT-PCR验证BUB1在肿瘤组织和癌旁组织中的表达水平，及其与CASC5表达水平的相关性。

结果

与癌旁组织相比，肿瘤组织中CASC5表达水平升高（

0.05），CASC5表达水平与患者TNM分期、淋巴结转移相关（

0.05）。与si-NC组相比，si-CASC5组MDA-MB-231和MCF-7细胞中CASC5表达水平降低（

0.05），细胞增殖能力及侵袭能力减弱（

0.05）。生物信息学预测CASC5可能与BUB1、NSL1、NDC80和MIS12等相互作用。与si-NC组相比，si-CASC5组MDA-MB-231细胞中BUB1表达水平降低（

0.05），NSL1、NDC80和MIS12表达水平无统计学差异（

0.05）。CASC5免疫沉淀产物中可检测到BUB1蛋白，BUB1免疫沉淀产物中可检测到CASC5蛋白。与si-NC组相比，si-BUB1组MDA-MB-231细胞中BUB1表达水平降低（

0.05），细胞增殖能力及侵袭能力减弱（

0.05）。与癌旁组织相比，肿瘤组织中BUB1表达水平升高（

0.05），CASC5表达水平与BUB1表达水平呈正相关（

=0.481 5）。

结论

CASC5可通过与BUB1相互作用，调控BUB1蛋白表达从而促进乳腺癌发生发展。

Abstract

Objective

To investigate the role of cancer susceptibility candidate 5 （CASC5） in the development of breast cancer and its related mechanisms.

Methods

Tumor tissues and paracancerous tissues from 50 breast cancer patients were collected，and the expression level of CASC5 was detected by qRT-PCR and its relationship with clinicopathological features was analyzed. si-CASC5，si-BUB1 and si-NC were transfected into MDA-MB-231 and MCF-7 cells by liposome transfection. The expression levels of cellular CASC5 and BUB1 were detected by qRT-PCR and Western blot，the proliferation ability of cells was detected by CCK-8 and the invasion ability of cells was detected by Transwell. CASC5-related proteins were analyzed by the String database and verified in MCF7 cells. Binding of CASC5 to BUB1 was detected by immunoprecipitation. qRT-PCR was used to verify the expression levels of BUB1 in tumor tissues and paracancerous tissues，and its correlation with the expression level of CASC5.

Results

Compared with paracancerous tissues，the expression level of CASC5 in tumor tissues was increased （

0.05），and the expression level of CASC5 was correlated with TNM stage and lymph node metastasis （

0.05）. Compared with si-NC group，the expression level of CASC5 in MDA-MB-231 and MCF-7 cells of si-CASC5 group was decreased （

0.05），the cell proliferation ability and the cell invasion ability were both decreased （

0.05）. Bioinformatics predicted that CASC5 may interact with BUB1，NSL1，NDC80 and MIS12. Compared with si-NC group，the expression level of BUB1 in MDA-MB-231 cells of si-CASC5 group was decreased（

0.05），and the expression levels of NSL1，NDC80 and MIS12 were not significantly different（

0.05）.BUB1 protein was detected in the immunoprecipitation product of CASC5，and CASC5 protein was detected in the immunoprecipitation product of BUB1. Compared with si-NC group，the expression level of BUB1 in MDA-MB-231 cells of si-BUB1 group was decreased（

0.05），the cell proliferation ability and the cell invasion ability were both decreased（

0.05）.The expression level of BUB1 in tumor tissues was increased compared with that in paracancerous tissues （

0.05），and the expression level of CASC5 was positively correlated with the expression level of BUB1（

=0.481 5）.

Conclusion

CASC5 can regulate the expression of BUB1 protein by interacting with BUB1 to promote the development of breast cancer.

关键词

乳腺癌易感性癌症候选基因5BUB1免疫共沉淀

Keywords

breast cancercancer susceptibility candidate 5BUB1immunoprecipitation

references

Ferlay J，Colombet M，Soerjomataram I，et al.Cancer statistics for the year 2020：an overview［J］.Int J Cancer，2021，149：778-789.doi： 10.1002/ijc.33588http://dx.doi.org/10.1002/ijc.33588.

Zheng Y，Jiang X，Wang M，et al.BMPR1B polymorphisms （rs1434536 and rs1970801） are associated with breast cancer susceptibility in Northwest Chinese Han females：a case-control study［J］.Clin Breast Cancer，2022，22（5）：e641-e646.doi： 10.1016/j.clbc. 2022.02.011http://dx.doi.org/10.1016/j.clbc.2022.02.011.

Mubarik S，Yu Y，Wang F，et al.Epidemiological and sociodemographic transitions of female breast cancer incidence，death，case fatality and DALYs in 21 world regions and globally，from 1990 to 2017：an age-period-cohort analysis［J］.J Adv Res，2021，37：185-196.doi： 10.1016/j.jare.2021.07.012http://dx.doi.org/10.1016/j.jare.2021.07.012.

Yue W，Wang Y，Meng TG，et al.Kinetochore scaffold 1 regulates SAC function during mouse oocyte meiotic maturation［J］.FASEB J，2022，36（3）：e22210.doi： 10.1096/fj.202101586RRhttp://dx.doi.org/10.1096/fj.202101586RR.

Singh PK，Bhatt MLB，Singh P，et al.CASC5 is a potential cancer-testis gene in human urinary bladder transitional cell carcinoma［J］.Drug Discov Ther，2021，15（6）：331-336.doi： 10.5582/ddt.2021http://dx.doi.org/10.5582/ddt.2021.

Shi Y，Gao S，Zheng Y，et al.LncRNA CASC15 functions as an unfavorable predictor of ovarian cancer prognosis and inhibits tumor progression through regulation of miR-221/ARID1A axis［J］.Onco Targets Ther，2019，12：8725-8736.doi： 10.2147/OTT.S219900http://dx.doi.org/10.2147/OTT.S219900.

Cui Y，Zhang C，Ma S，et al.CASC5 is a potential tumor driving gene in lung adenocarcinoma［J］.Cell Biochem Funct，2020，38（6）：733-742.doi： 10.1002/cbf.3540http://dx.doi.org/10.1002/cbf.3540.

Fu Y，Zhou QZ，Zhang XL，et al.Identification of hub genes using co-expression network analysis in breast cancer as a tool to predict different stages［J］.Med Sci Monit，2019，25：8873-8890.doi： 10.12659/MSM.919046http://dx.doi.org/10.12659/MSM.919046.

Yu H，Zhang S，Ibrahim AN，et al.Retraction notice to "Serine/threonine kinase BUB1 promotes proliferation and radio-resistance in glioblastoma"［J］.Pathol Res Pract，2022，233：153889.doi： 10.1016/j.prp.2022.153889http://dx.doi.org/10.1016/j.prp.2022.153889.

Shagisultanova E，Gao D，Callihan E，et al.Overall survival is the lowest among young women with postpartum breast cancer ［J］.Eur J Cancer，2022，168：119-127.doi： 10.1016/j.ejca.2022.03.014http://dx.doi.org/10.1016/j.ejca.2022.03.014.

Takimoto M.D40/KNL1/CASC5 and autosomal recessive primary microcephaly［J］.Congenit Anom （Kyoto），2017，57（6）：191-196.doi： 10.1111/cga.12252http://dx.doi.org/10.1111/cga.12252.

Saadi A，Verny F，Siquier-Pernet K，et al.Refining the phenotype associated with CASC5 mutation［J］.Neurogenetics，2016，17（1）：71-78.doi： 10.1007/s10048-015-0468-7http://dx.doi.org/10.1007/s10048-015-0468-7.

Akiyama Y，Komiyama M，Miyata H，et al.Novel cancer-testis antigen expression on glioma cell lines derived from high-grade glioma patients［J］.Oncol Rep，2014，31（4）：1683-1690.doi： 10.3892/or.2014.3049http://dx.doi.org/10.3892/or.2014.3049.

Urata YN，Takeshita F，Tanaka H，et al.Targeted knockdown of the kinetochore protein D40/Knl-1 inhibits human cancer in a p53 status-independent manner［J］.Sci Rep，2015，5：13676.doi： 10.1038/srep13676http://dx.doi.org/10.1038/srep13676.

Koyuncu D，Sharma U，Goka ET，et al.Spindle assembly checkpoint gene BUB1B is essential in breast cancer cell survival［J］.Breast Cancer Res Treat，2021，185（2）：331-341.doi： 10.1007/s10549-020-05962-2http://dx.doi.org/10.1007/s10549-020-05962-2.

Sun SC，Kim NH.Spindle assembly checkpoint and its regulators in meiosis［J］.Hum Reprod Update，2012，18（1）：60-72.doi： 10.1093/humupd/dmr044http://dx.doi.org/10.1093/humupd/dmr044.

Elahi E，Suraweera N，Volikos E，et al.Five quantitative trait loci control radiation-induced adenoma multiplicity in Mom1R Apc Min/+ mice［J］.PLoS One，2009，4（2）：e4388.doi： 10.1371/journal.pone.0004388http://dx.doi.org/10.1371/journal.pone.0004388.

Zhu LJ，Pan Y，Chen XY，et al.BUB1 promotes proliferation of liver cancer cells by activating SMAD2 phosphorylation［J］.Oncol Lett，2020，19（5）：3506-3512.doi： 10.3892/ol.2020.11445http://dx.doi.org/10.3892/ol.2020.11445.

Qiu J，Zhang S，Wang P，et al.BUB1B promotes hepatocellular carcinoma progression via activation of the mTORC1 signaling pathway［J］.Cancer Med，2020，9（21）：8159-8172.doi： 10.1002/cam4.3411http://dx.doi.org/10.1002/cam4.3411.

Fu X，Chen G，Cai ZD，et al.Overexpression of BUB1B contributes to progression of prostate cancer and predicts poor outcome in patients with prostate cancer［J］.Onco Targets Ther，2016，9：2211-2220.doi： 10.2147/OTT.S101994http://dx.doi.org/10.2147/OTT.S101994.

Piao J，Zhu L，Sun J，et al.High expression of CDK1 and BUB1 predicts poor prognosis of pancreatic ductal adenocarcinoma［J］.Gene，2019，701：15-22.doi： 10.1016/j.gene.2019.02.081http://dx.doi.org/10.1016/j.gene.2019.02.081.

Zhang G，Lischetti T，Nilsson J.A minimal number of MELT repeats supports all the functions of KNL1 in chromosome segregation［J］.J Cell Sci，2014，127（Pt 4）：871-884.doi： 10.1242/jcs.139725http://dx.doi.org/10.1242/jcs.139725.

Vleugel M，Omerzu M，Groenewold V，et al.Sequential multisite phospho-regulation of KNL1-BUB3 interfaces at mitotic kinetochores［J］.Mol Cell，2015，57（5）：824-835.doi：10.1016/j.molcel. 2014.12.036http://dx.doi.org/10.1016/j.molcel.2014.12.036.

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